Imlygic (Talimogene laherparepvec) is a biopharmaceutical drug. It is a genetically modified form of Herpes simplex virus (HSV-1) that is made less virulent and possesses anti-cancer properties. It is the first and probably the only FDA-approved viral therapy for the treatment of melanoma [Ref].

Indications of Imlygic (Talimogene laherparepvec):

• Unresectable melanoma:

  • It is indicated for treating unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after the initial surgery
  • Limitations of use: Improvement of overall survival or effect on visceral metastases is not seen.

Imlygic (Talimogene laherparepvec) dose in adults:

Note:

It may not be possible to inject all lesions at each treatment visit or over the full course of treatment. Previously injected /untreated lesions may be injected at subsequent visits.

Imlygic (Talimogene laherparepvec) dose in the treatment of unresectable Melanoma:

• Intralesional:

  • Maximum volume (per treatment visit, for all injected lesions combined): 4 mL.
  • Continue treatment for at least 6 months unless another therapy is necessary or until there are no injectable lesions to treat, treatment should be restarted in case of new unresectable lesions.

• Use the following to determine the volume of talimogene laherparepvec to be injected

  • If the lesion size is >5 cm, inject up to 4 mL
  • If the lesion size is >2.5 cm to 5 cm, inject up to 2 mL
  • If the lesion size is >1.5 cm to 2.5 cm, inject up to 1 mL
  • If the lesion size is >0.5 cm to 1.5 cm, inject up to 0.5 mL
  • If the lesion size is ≤0.5 cm, inject up to 0.1 mL

• Initial treatment visit:

  • Inject up to 4 mL at a concentration of 10 (1 million) PFU/mL.
  • Lesions should be treated according to size(starting from the largest) until maximum injection volume is reached or all lesions are treated.

• Second treatment visit (3 weeks after initial treatment):

  • Inject up to 4 mL at a concentration of 10 (100 million) PFU/mL.
  • Any new lesion should be treated first and remaining lesions based on lesion size until maximum injection volume is reached or all lesions have been treated.

• All subsequent treatment visits, including reinitiation (2 weeks after previous treatment):

  • Inject up to 4 mL at a concentration of 10 (100 million) PFU/mL.
  • Any new lesion should be injected first and the remaining lesions based on lesion size until maximum injection volume is reached or all lesions have been treated.

Dose in Children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Category: X

• It is not recommended during pregnancy.
• Talimogene Laherparepvec (GMO-modified herpes simplex virus Type 1 (HSV-1), is a live, attenuated and genetically modified herpesvirus type 1.
• It can cross the placenta, cause infections in the neonate, and can also be transmitted during pregnancy.
• Women who are pregnant should not come in contact with patients receiving talimogene laherparepvec.
• Effective contraception should be used by women during therapy.

Use of Talimogene laherparepvec during breastfeeding

• It is unknown if Talimogene laherparepvec is excreted in breast milk.
• Manufacturers recommend that you stop breastfeeding. The importance of the treatment for the mother is considered.

Dosage adjustment in renal disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.

Dosage adjustment in liver disease:

• There are no dosage adjustments provided in the manufacturer’s labeling.

Common Side Effects of Imlygic (Talimogene laherparepvec):

• Central Nervous System:

  • Fatigue
  • Chills
  • Headache

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Diarrhea
  • Constipation

• Local:

  • Pain At Injection Site

• Neuromuscular & Skeletal:

  • Myalgia
  • Arthralgia
  • Limb Pain

• Respiratory:

  • Flu-Like Symptoms

• Miscellaneous:

  • Fever

Uncommon Side Effects of Imlygic (Talimogene laherparepvec):

• Central Nervous System:

  • Dizziness

• Endocrine & Metabolic:

  • Weight Loss

• Gastrointestinal:

  • Abdominal Pain

• Respiratory:

  • Oropharyngeal Pain

Rare Side effects of Imlygic (Talimogene laherparepvec):

• Cardiovascular:

  • Deep Vein Thrombosis
  • Vasculitis

• Dermatologic:

  • Cellulitis
  • Dermatitis
  • Exacerbation Of Psoriasis
  • Skin Rash
  • Vitiligo

• Gastrointestinal:

  • Oral Herpes

• Infection:

  • Bacterial Infection (Systemic)
  • Herpes Virus Infection

• Ophthalmic:

  • Herpes Simplex Keratitis

• Renal:

  • Glomerulonephritis

• Respiratory:

  • Acute Asthma
  • Pneumonitis

Contraindication to Imlygic (Talimogene laherparepvec):

• Pregnancy
• Patients with immunocompromised conditions
• Leukemia
• Lymphoma
• AIDS
• Patients receiving immunosuppressive therapy

Warnings and precautions

• Immune-mediated events

  • It is possible for immune-mediated events like glomerulonephritis and pneumonitis to occur. Therefore, it is important to be vigilant.

• Infection

  • Cold sores, herpetic keratitis, and disseminated herpetic infected patients with immunocompromised can all occur.
  • To prevent the transmission of viruses to herpetic lesions, it is important to follow standard practice.

• Complications at the injection site:

  • Injection-site complications, such as necrosis, cellulitis, tumor tissue ulceration, impaired healing, or systemic bacteria infection, may arise during treatment with talimogene talimogene talepvec.
  • Previous radiation to the injection site, or lesions in areas that are not well vascularized, can increase the risk of impaired wound healing.

• Toxicity in the lungs:

  • With prolonged use, it can lead to obstructive lung disease. Therefore, you should be vigilant.

• Multiple myeloma

  • A plasmacytoma was found near the laherparepvec injection location in patients with smoldering multimyeloma.

Talimogene laherparepvec: Drug Interaction

Monitoring parameters:

• Immune mediated reactions
• Injection site complications
• Obstructive airway disease
• Signs/symptoms of herpetic infections

How to administer Imlygic (Talimogene laherparepvec)?

• Clean the lesion and its surrounding areas with alcohol.
• Dry them. If necessary, you can inject local anesthetic agents peripherally at the injection site.
• An intralesional injection is made into any cutaneous, subcutaneous, or nodal lesions visible on ultrasound.
• Talimogene leparepvec is injected using a 22-26 gauge needle.
• If the lesion is more than the needle's radial reach, multiple tracks are used to disperse the drug.
• Talimogene laherparepvec must be injected evenly and fully within the lesion.
• The needle should not be removed from the lesion. To prevent leakage, the needle should be gently removed from the lesion. 
• You can repeat the process for any other lesions. Each time a new lesion is injected, a new needle must be used. 
• After the injection is complete, you should apply pressure for no less than 30 seconds.
• The surrounding area should also be cleaned with alcohol. After changing gloves, cover the lesion with an absorbent pad.
• Dry the occlusive dressing with a dry towel. Wipe the outside of the dressing with alcohol.
• Cover the injection site for 7 days or more after each treatment. If there is any weeping or oozing, it should be covered.
• Pregnant or immunocompromised women should not prepare or give talimogene lherparepvec.
• They should also avoid direct contact with the skin, dressings or fluids of patients being treated.
• For administration, biohazard precautions (personal protection equipment) should be taken. 
• Useful dressings and cleaning products should be stored in a plastic bag and disposed with your household waste.

Mechanism of action of Talimogene laherparepvec (Imlygic):

• Talimogene Laherparepvec, a genetically modified oncolytic herpes simplex virus (HSV1) oncolytic virus, acts by selective replication.
• Modification of Talimogene Laherparepvec is possible by the deletion of two non-essential viral genes.
• Eliminating the ICP34.5 herpesvirus neurovirulence factor gene leads to decreased viral pathogenicity and enhanced tumor-selective reproduction.
• It also results in the deletion of ICP47 genes, reduction of virally-mediated suppression of antigen presentations and an increase in expression of HSV US11 genes.
• Virally derived GM–CSF activates the anti-tumor cells and activates them.

Time to reach peak:

• Urine containing the highest levels of talimogene, laherparepvec was detected on the day of treatment

International Brands of Talimogene laherparepvec:

• Imlygic

Talimogene laherparepvec Brand Names in Pakistan:

No Brands Available in Pakistan.